TY - JOUR
T1 - Glucan binding protein C of Streptococcus mutans mediates both sucrose-independent and sucrose-dependent adherence
AU - Mieher, Joshua L.
AU - Larson, Matthew R.
AU - Schormann, Norbert
AU - Purushotham, Sangeetha
AU - Wu, Ren
AU - Rajashankar, Kanagalaghatta R.
AU - Wu, Hui
AU - Deivanayagam, Champion
N1 - Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen Streptococcus mutans, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for S. mutans. Despite the structural similarities with S. mutans antigen I/II (AgI/II) and SspB of Streptococcus gordonii, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (β-D-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.
AB - The high-resolution structure of glucan binding protein C (GbpC) at 1.14 Å, a sucrose-dependent virulence factor of the dental caries pathogen Streptococcus mutans, has been determined. GbpC shares not only structural similarities with the V regions of AgI/II and SspB but also functional adherence to salivary agglutinin (SAG) and its scavenger receptor cysteine-rich domains (SRCRs). This is not only a newly identified function for GbpC but also an additional fail-safe binding mechanism for S. mutans. Despite the structural similarities with S. mutans antigen I/II (AgI/II) and SspB of Streptococcus gordonii, GbpC remains unique among these surface proteins in its propensity to adhere to dextran/glucans. The complex crystal structure of GbpC with dextrose (β-D-glucose; Protein Data Bank ligand BGC) highlights exclusive structural features that facilitate this interaction with dextran. Targeted deletion mutant studies on GbpC's divergent loop region in the vicinity of a highly conserved calcium binding site confirm its role in biofilm formation. Finally, we present a model for adherence to dextran. The structure of GbpC highlights how artfully microbes have engineered the lectin-like folds to broaden their functional adherence repertoire.
KW - Antigen I/II
KW - Fibrillar
KW - Glucan binding protein
KW - Lectin-like fold
KW - Microbial adherence
KW - Polyproline type II helix
KW - Salivary agglutinin
KW - Streptococcus gordonii
KW - Streptococcus mutans
KW - Sucrose-dependent adhesion
KW - Sucrose-independent adhesion
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U2 - 10.1128/IAI.00146-18
DO - 10.1128/IAI.00146-18
M3 - Article
C2 - 29685986
AN - SCOPUS:85050150647
SN - 0019-9567
VL - 86
JO - Infection and Immunity
JF - Infection and Immunity
IS - 7
M1 - e00146-18
ER -